Y. Jimbo

The University of Tokyo, Tokyo, Tokyo-to, Japan

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Publications (34)49.38 Total impact

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    ABSTRACT: Light addressing is an emerging and sophisticated technique that can induce pinpoint and/or patterned neuronal activation in cultured neurons. We previously developed a light-addressable electrode using hydrogenated amorphous silicon (a-Si:H), which was sandwiched between a tin oxide (SnO(2)) substrate and a passivation layer of zinc antimonate (ZnOSb(2)O(5)) dispersed epoxy. This research developed an experimental system that simultaneously implemented light-addressed stimulation and Ca(2+) imaging of neuronal activities. The translucent and thin laminated structure of our electrode permitted optical accesses from two directions: Ca(2+) imaging from above and light addressing from beneath. The submillisecond bright/dark switching property of our electrode offered light-addressed stimulation without causing interference with Ca(2+) imaging. To provide patterned illumination for light addressing, a digital micromirror device was installed in the system as an active photomask. The system could induce pinpoint neuronal activation at a cellular level.
    IEEE transactions on bio-medical engineering 07/2009; 56(11):2660-5. · 2.15 Impact Factor
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    ABSTRACT: This paper describes an advanced Micro Channel Array (MCA) so as to record neuronal network at multiple points simultaneously. Developed MCA is designed for neuronal network analysis which has been studied by co-authors using MEA (Micro Electrode Arrays) system. The MCA employs the principle of the extracellular recording. Presented MCA has the following advantages. First of all, the electrodes integrated around individual micro channels are electrically isolated for parallel multipoint recording. Sucking and clamping of cells through micro channels is expected to improve the cellular selectivity and S/N ratio. In this study, hippocampal neurons were cultured on the developed MCA. As a result, the spontaneous and evoked spike potential could be recorded by sucking and clamping the cells at multiple points. Herein, we describe the successful experimental results together with the design and fabrication of the advanced MCA toward on-chip analysis of neuronal network.
    Conference proceedings: ... Annual International Conference of the IEEE Engineering in Medicine and Biology Society. IEEE Engineering in Medicine and Biology Society. Conference 02/2008; 2008:943-6.
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    Y Jimbo
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    ABSTRACT: Based on the advantages of MEA-based recording, developmental changes of spontaneous activity and tetanus-induced modification of evoked activity were studied. Rat cortical neurons were cultured on MEAs and the spontaneous activity was continuously monitored for two months. The activity started a few days after plating. During the second week, the cultures generated periodic synchronized bursts, which were the characteristic properties of cortical neurons in vitro. In about one month, the cultured networks reached a steady state. Between these two, we found a critical period during which only weak activities were generated. This critical period might reflect the transition from immature networks to mature networks including precisely controlled excitatory and inhibitory synapses. We could elicit clear evoked responses with high reproducibility in mature cultures. A focal tetanic stimulation was applied to the mature cultures and how the tetanus affects 64 kinds of evoked activity was studied. The evoked responses showed bi-directional changes in their propagation patterns, potentiation and depression. These induced changes reflected the correlation properties with the tetanized activity pattern. The next step will be the combination of long-term recording and multi-site stimulation. How long does the induced change last, as well as how additional strong activity affects the previously induced changes, will be studied.
    Archives italiennes de biologie 12/2007; 145(3-4):289-97. · 1.43 Impact Factor
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    ABSTRACT: Spontaneous electrical activity and intracellular calcium dynamics in dense cultures of rat cortical networks were simultaneously observed by using microelectrode array (MEA) and optical imaging system. At around one-week-cultures, periodical synchronized bursts, which are characteristic features of cultured cortical networks, were observed, and these synchronized bursts were followed by synchronized intracellular calcium transients among neural cells. After three weeks cultures, synchronized intracellular calcium transients were rarely observed in the cultured cortical networks although neurons showed distinct electrical activity with high frequency. As for the intermediate stage between these two states, we found slow, radial propagation of intracellular calcium waves were observed independent of the electrical activity of neural cells at around two-weeks cultures. The carriers of these calcium waves were suggested to be astrocytes from the result of pharmacological treatments of these cultured cortical networks. These results indicate that the dynamics of intracellular calcium in cortical networks changes depending on the developmental stages of cortical tissues, and astrocytes have characteristic roles in the development of functional cortical tissues as well as the spontaneous electrical activity of neurons.
    Neural Engineering, 2007. CNE '07. 3rd International IEEE/EMBS Conference on; 06/2007
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    ABSTRACT: In the attempt to fully understand the mechanism for the formation and realization of tissue-specific functions of living multicellular systems, a couple of experimental conditions is required; grasping both the whole picture and the state of elements of a multicellular system. From this viewpoint, selecting neuronal circuits as the target, we have developed an electrical recording method from cultured small neuronal circuits by combining a simple micropatterning technique with a extracellular recording method using a mobile microelectrode. The simple micropatterning method enabled formation of thousands of individual small neuronal circuits consist of single to tens of neurons in one common 35-mm culture dish without any microfabrication apparatus by means of spraying of poly-D-lysine solution onto non-adhesive culture surfaces. Those small neuronal circuits, derived from embryonic hippocampus of rats, showed spontaneous synchronous firing after 8 days after cell seeding. Any of these small neuronal circuits were accessible with a mobile microelectrode, and their spontaneous firings were recorded noninvasively with single-cell-resolution by positioning the tip on constituent neurons. This set of methods does not require any specialized microfabrication apparatus or chemicals, and has a possibility to be used as a practical recording method of electrophysiological activities of a variety of multicellular organisms
    Neural Engineering, 2007. CNE '07. 3rd International IEEE/EMBS Conference on; 06/2007
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    ABSTRACT: In order to probe the spatio-temporal activity of cultured neural network, microelectrode arrays (MEAs) have been widely used. MEAs, however, have limitations of their electrode numbers and densities, resulting in low spatial resolutions of stimulation and recording. Here, to overcome this problem, we propose and develop an experimental setup for light-addressed stimulation and simultaneous fluorescence calcium imaging, using the previously published light-addressable electrode. The electrode has a translucent thin-film-laminated structure and allows optical access from both sides of the substrate. We, thus, provided the fluorescence excitation light from the topside and an addressing illumination from the bottom. By instantly shutting out the fluorescence excitation light during the stimulus application, we prevented the excitation light from interfering with the addressing illumination. With this experimental setup, we successfully measured spatio-temporal patterns of neuronal activities evoked by light-addressed stimuli. Evoked fluorescence transients with hundred-millisecond latencies suggested the possibility that some neurons were activated by recurrent synaptic inputs, which were possibly overlooked by previous MEA studies.
    Neural Engineering, 2007. CNE '07. 3rd International IEEE/EMBS Conference on; 06/2007
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    ABSTRACT: This paper describes a new type of MCA (micro channel array) for simultaneous multipoint measurement of cellular network. Presented MCA is designed for advanced neural network analysis which has been studied by co-authors using 64 ch MEA (micro electrode arrays) system. First of all, sucking and clamping of cells through channels of developed MCA is expected to improve electrophysiological signal detections. Electrophysiological sensing electrodes integrated around individual channels of MCA are electrically isolated for simultaneous multipoint measurement.
    01/2007;
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    ABSTRACT: We studied the effects of carbachol, a cholinergic agonist, on extracellularly evoked firing of networks in mature cultures of rat cortical neurons, using multi-electrode arrays to monitor the activity of large numbers of neurons simultaneously. These cultures show evoked burst firing which propagates through dense synaptic connections. When a brief voltage pulse was applied to one extracellular electrode, spiking electrical responses were evoked in neurons throughout the network. The response had two components: an early phase, terminating within 30-80 ms, and a late phase which could last several hundreds of milliseconds. Action potentials evoked during the early phase were precisely timed, with only small jitter. In contrast, the late phase characteristically showed clusters of electrical activity with significant spatio-temporal fluctuations. The late phase was suppressed by applying a relatively small amount of carbachol (5 microM) in the external solution, even though the spontaneous firing rate was not significantly changed. Carbachol increased both the spike-timing precision and the speed of propagation of population spikes, and selectively increased the firing coincidence in a subset of neuron pairs in the network, while suppressing late variable firing in responses. Hence, the results give quantitative support for the idea that cholinergic activation in the cortex has a general role of focusing or enhancing significant associative firing of neurons.
    Neuroscience 02/2005; 134(2):439-48. · 3.12 Impact Factor
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    ABSTRACT: Activation of the cholinergic innervation of the cortex has been implicated in sensory processing, learning, and memory. At the cellular level, acetylcholine both increases excitability and depresses synaptic transmission, and its effects on network firing are hard to predict. We studied the effects of carbachol, a cholinergic agonist, on network firing in cultures of rat cortical neurons, using electrode arrays to monitor the activity of large numbers of neurons simultaneously. These cultures show stable spontaneous synchronized burst firing which propagates through dense synaptic connections. Carbachol (10-50 microM), acting through muscarinic receptors, was found to induce a switch to asynchronous single-spike firing and to result in a loss of regularity and fragmentation of the burst structure. To obtain a quantitative measure of cholinergic actions on cortical networks, we applied a cluster Poisson-process model to sets of paralleled spike-trains in the presence and absence of carbachol. This revealed that the time series can be well-characterized by such a simple model, consistent with the observed 1/f(b)-like spectra (0.04<b<2.08). After applying higher concentrations of carbachol the property of the spectra shifted toward a Poisson-process (white) spectrum. These results indicate that cholinergic neurotransmitters have a strong and reliable desynchronizing action on cortical neural activity.
    Neuroscience 01/2005; 134(2):425-37. · 3.12 Impact Factor
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    ABSTRACT: We investigated cholinergic modulation effects on synchronized burst activity of neurons in rat dissociated cortical cultures on electrode arrays, using a cholinergic agonist, carbachol (CCh). Application of CCh resulted in a loss of regularity, a less precise synchronization, and a fragmentation of the burst structure. We found that temporal properties of spike trains were well-characterized by a simple Poisson cluster-process model, which provided a precise insight into the temporal structure of spike trains and allowed quantitative fitting of the spectral changes induced by CCh. These results should help to elucidate the complex actions of cholinergic modulation on cortical cells in intact neural networks.
    Neural Networks, 2004. Proceedings. 2004 IEEE International Joint Conference on; 08/2004
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    ABSTRACT: A new type of individual-cell-based on-chip multielectrode array (MEA) cell-cultivation system with an agarose microchamber (AMC) array for topographical control of the network patterns of a living neuronal network has been developed. The advantages of this system are that it allows control of the cell positions and numbers for cultivation using AMCs, as well as easy and flexible control of the pattern of connections between the AMCs through photothermal etching where a portion of the agarose layer is melted with a 1480 nm infrared laser beam. With adequate laser power, narrow micrometer-order grooves (microchannels) can easily be fabricated that can be used to combine neighbouring AMCs to enable topographical control of the neural network pattern. Using this system, an individual-cell-based neural network pattern was formed of rat hippocampal cells within the AMC array without cells escaping from the electrode positions in the microchamber during an eight-day cultivation, and could record cell firing in response to 1.5 V, 500 kHz stimulation through an electrode. This demonstrated the potential of the on-chip AMCMEA cell cultivation system for long-term single-cell-based electrophysiological measurement of a neural network system.
    IEE Proceedings - Nanobiotechnology 07/2004; 151(3):116-21. · 1.82 Impact Factor
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    ABSTRACT: Not Available
    Microprocesses and Nanotechnology Conference, 2004. Digest of Papers. 2004 International; 02/2004
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    ABSTRACT: The capability for multisite stimulation is one of the biggest potential advantages of microelectrode arrays (MEAs). There remain, however, several technical problems which have hindered the development of a practical stimulation system. An important design goal is to allow programmable multisite stimulation, which produces minimal interference with simultaneous extracellular and patch or whole cell clamp recording. Here, we describe a multisite stimulation and recording system with novel interface circuit modules, in which preamplifiers and transistor transistor logic-driven solid-state switching devices are integrated. This integration permits PC-controlled remote switching of each substrate electrode. This allows not only flexible selection of stimulation sites, but also rapid switching of the selected sites between stimulation and recording, within 1.2 ms. This allowed almost continuous monitoring of extracellular signals at all the substrate-embedded electrodes, including those used for stimulation. In addition, the vibration-free solid-state switching made it possible to record whole-cell synaptic currents in one neuron, evoked from multiple sites in the network. We have used this system to visualize spatial propagation patterns of evoked responses in cultured networks of cortical neurons. This MEA-based stimulation system is a useful tool for studying neuronal signal processing in biological neuronal networks, as well as the process of synaptic integration within single neurons.
    IEEE Transactions on Biomedical Engineering 03/2003; · 2.35 Impact Factor
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    ABSTRACT: We have developed a new type of on-chip cell cultivation system using an agarose microchamber (AMC) array and a photo-thermal etching method, thus enabling topographical control of neuronal network pattern step-by-step during cell cultivation. By using photo-thermal etching (micro melting) method, the number of microtunnel connecting microchambers can be easily increased, even during cell cultivation, according to the progress of the neuronal network formation. To demonstrate the capability of this system for topographical control of network formation, we cultured hippocampal neurons in this AMC array. We found that the cells in microchambers made fiber connections through microtunnels. Furthermore the cells even made fiber connections through additional microtunnels fabricated during cultivation by photo-thermal etching. The results showed that the photo-thermal etching could be used during cultivation without damaging cells.
    01/2003;
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    ABSTRACT: A multichannel glutamate sensor was fabricated that consists of enzyme modified electrodes and has a high sensitivity and selectivity to glutamate. We placed a rat hippocampal slice on the sensor and monitored the current at four electrodes resulting from the stimulation with muscimol, a gamma-aminobutyric acid(A) (GABA(A)) receptor agonist. We obtained different glutamate concentration increases at the different positions, suppressed by bicuculline, a GABA(A) receptor antagonist. This demonstrated that the sensor can monitor the glutamate released via GABA(A) receptors pathways, and the difference in the concentrations may indicate differences in the distribution of GABA(A) receptor as well as diverse receptor functions. This multichannel sensor may be useful for non-invasive, real-time monitoring of glutamate distribution, which would make it a valuable tool for pharmacological analysis.
    Neuroscience Letters 06/2001; 304(1-2):112-6. · 2.03 Impact Factor
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    ABSTRACT: Neuronal networks of dissociated cortical neurons from neonatal rats were cultured over a multielectrode dish with 64 active sites, which were used both for recording the electrical activity and for stimulation. After about 4 weeks of culture, a dense network of neurons had developed and their electrical activity was studied. When a brief voltage pulse was applied to one extracellular electrode, a clear electrical response was evoked over almost the entire network. When a strong voltage pulse was used, the response was composed of an early phase, terminating within 25 ms, and a late phase which could last several hundreds of milliseconds. Action potentials evoked during the early phase occurred with a precise timing with a small jitter and the electrical activity initiated by a localized stimulation diffused significantly over the network. In contrast, the late phase was characterized by the occurrence of clusters of electrical activity with significant spatio-temporal fluctuations. The late phase was suppressed by adding small amounts of D(-)-2-amino-5-phosphonovaleric acid to the extracellular medium, or by increasing the amount of extracellular Mg2+. The electrical activity of the network was substantially increased by the addition of bicuculline to the extracellular medium. The results presented here show that the neuronal network may exist in two different dynamical states: one state in which the neuronal network behaves as a non-chaotic deterministic system and another state where the system exhibits large spatio-temporal fluctuations, characteristic of stochastic or chaotic systems.
    Biological Cybernetics 08/2000; 83(1):1-20. · 2.07 Impact Factor
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    Y Jimbo, H P Robinson
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    ABSTRACT: The spatial propagation of synchronized activity in cortical slice cultures was characterized by multi-site extracellular recording. Spontaneous activity was studied in normal culture medium, and in bicuculline- or kainic acid-containing media. A common feature in all these conditions was that activity was generated first in superficial layers (i.e., layer I/II) before spreading over the whole area of the slice. In culture medium or bicuculline-containing medium, the initiation site of the activity was not constant and showed a large variety of patterns of horizontal propagation. Kainic acid induced epileptiform activity, consisting of intense initial bursts followed by repetitive after-discharges. Though the patterns of spatial propagation of the bursts were variable as in the other conditions, the after-discharges followed a constant path. Cross-correlation analysis indicated that the network moved in a graded fashion to a steady state during the sequence of after-discharges.
    Bioelectrochemistry 07/2000; 51(2):107-15. · 3.95 Impact Factor
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    ABSTRACT: Activity-dependent modification of synaptic efficacy is widely recognized as a cellular basis of learning, memory, and developmental plasticity. Little is known, however, of the consequences of such modification on network activity. Using electrode arrays, we examined how a single, localized tetanic stimulus affects the firing of up to 72 neurons recorded simultaneously in cultured networks of cortical neurons, in response to activation through 64 different test stimulus pathways. The same tetanus produced potentiated transmission in some stimulus pathways and depressed transmission in others. Unexpectedly, responses were homogeneous: for any one stimulus pathway, neuronal responses were either all enhanced or all depressed. Cross-correlation of responses with the responses elicited through the tetanized site revealed that both enhanced and depressed responses followed a common principle: activity that was closely correlated before tetanus with spikes elicited through the tetanized pathway was enhanced, whereas activity outside a 40-ms time window of correlation to tetanic pathway spikes was depressed. Response homogeneity could result from pathway-specific recurrently excitatory circuits, whose gain is increased or decreased by the tetanus, according to its cross-correlation with the tetanized pathway response. The results show how spatial responses following localized tetanic stimuli, although complex, can be accounted for by a simple rule for activity-dependent modification.
    Biophysical Journal 03/1999; 76(2):670-8. · 3.67 Impact Factor
  • A. Kawana, Y. Jimbo
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    ABSTRACT: Neurointerfaces which connect the nervous system to electrical circuits are expected to play an important role in exploring the frontier of brain science. A planar electrode array (PEA) which is a useful neurointerface for observing electrical activity of cultured neuronal network is described. The developmental electrical activity changes of neuronal networks and electrical activity propagation in reconstructed visual system are observed successfully using the PEA. The possibility of formation of patterned neuronal network on the PEA are also shown using a novel cell positioning technique. The PEA is expected to play an important role in developing brain science
    Micro Electro Mechanical Systems, 1999. MEMS '99. Twelfth IEEE International Conference on; 02/1999
  • Y. Jimbo
    Biophysical Journal 02/1999; 76(2):670-678. · 3.67 Impact Factor

Publication Stats

1k Citations
49.38 Total Impact Points

Institutions

  • 1996–2007
    • The University of Tokyo
      • • Graduate School of Frontier Sciences
      • • Department of Precision Engineering
      • • College of Art and Science & Graduate School of Arts and Sciences
      • • Department of Pharmaceutical Sciences
      Tokyo, Tokyo-to, Japan
  • 2004–2005
    • University of Cambridge
      • Department of Physiology, Development and Neuroscience
      Cambridge, England, United Kingdom
  • 1993–2000
    • Nippon Telegraph and Telephone
      • NTT Basic Research Laboratories
      Edo, Tōkyō, Japan
    • NTT DOCOMO
      Edo, Tōkyō, Japan